PB2529: RENAL FUNCTIONS EVOLUTION OF 6 SCD PATIENTS TREATED BY L-GLUTAMINE PHARMACEUTICAL GRADE FOR 30 MONTHS: A REAL-WORLD STUDY.
Authors: Mohamed Yassin, Narcisse Elenga
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Sickle cell disease (SCD) is a rare genetic blood disorder that affects millions of people around the world. Oxidative stress is one of the key contributors to the pathophysiology of SCD and related complications. L-glutamine has been shown to play an important role in the regulation of oxidative stress by normalizing the altered NAD redox system in patients with SCD. In a Phase 3 clinical trial, L-glutamine demonstrated significant reduction in SCD acute complications with or without hydroxyurea (HU) use, over a 48-week period. Renal function impairment is a common complication of SCD and can have serious consequences for patients. Multiple studies have demonstrated a high prevalence of renal function impairment in SCD patients and associated with an increased risk of mortality. A recent long-term real-world study demonstrated that l-glutamine reduced the acute complications and the hemolysis markers of 19 patients after 30months of treatment. In this observational real-world study, we are reporting the long-term renal function evolution of 6 patients treated by L-glutamine for 30 months. Aims: To explore the renal function evolution of SCD patients treated with pharmaceutical-grade L-glutamine in pediatric and adult patients with SCD at follow-up time points of 12 and 30 months after initiation of treatment. Methods: Six patients (1 pediatric and 5 adults), with confirmed diagnosis of SCD (HbSS genotype) were treated with L-glutamine oral powder (~0.3 g/kg body weight, Endari®) twice daily for 30 months. 4 patients were from Qatar with the Arab-Indian haplotype and 2 patients were from French Guiana with the African haplotype. Clinical events and laboratory parameters were collected or measured at baseline, 12 and at 30 months. Baseline measures for VOCs was collected for the 12 months prior to L-glutamine initiation. Results: Four patients (all adults) were from Qatar with Arab Indian haplotype, whereas two patients (one pediatric and one adult) were from French Guiana with African haplotype. 100% compliance was reported for all patients under intervention. The study demonstrated that all patients who ceased to show any VOCs, at both 12 months and 30 months of treatment with L-glutamine, also showed significant improvements in blood parameters: the mean (SD) increase in hemoglobin concentrations was 0.48 (0.64) g/dL from baseline to 12 months while the mean (SD) from baseline to 30 months was 1.47 (0.77) g/dL. Mean (SD) reticulocyte counts and LDH levels decreased from baseline to 120 weeks (mean [SD] change from baseline to 120 weeks, reticulocyte counts: -88.83 [181.70] x109 cells/L; LDH levels: -408.00 [344.65] U/L). Regarding the renal function, the eGFR levels reduced from baseline to 12 months and 30 months (mean (SD) change from baseline to 12 months: -5.33 [15.32] mL/min/1.73m2; 30 months: -12.17 [22.08] mL/min/1.73m2). There were improvements observed in albumin creatinine ratio (ACR) from baseline to 12 months (mean [SD] ACR: -7.63 [11.33] mg/g) and 30 months (mean [SD] ACR: -17.62 [26.44] mg/g) consistent with an improvement in albuminuria from baseline to 12 months and 30 months (mean (SD) change from baseline to 12 months (-3.53 [2.88] mg/L; 30 months: -8.03 [7.15] mg/L). Improvements were also seen in both serum creatinine and urine creatinine levels from baseline to 12 months (mean [SD] serum creatinine: -0.50 [3.39] micromol/L; urine creatinine: -0.35 [0.62] micromol/L). Summary/Conclusion: This real-world study showed that, along with significant improvement in clinical outcomes and hemolysis, L-glutamine improved renal function of six SCD patients after 30 months of treatment. Moreover, this study highlighted that treating SCD patients for 30 months with L-glutamine was safe and did not alter patient renal functions.Keywords: Sickle cell disease, Hemoglobinopathy, Renal impairment, Hemoglobin